Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 345 24th Ave. North, Nashville, TN 37203, USA.
J Infect Dis. 2010 Jun 1;201(11):1703-7. doi: 10.1086/652419.
Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse-transcriptase inhibitors was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine whether nucleoside reverse-transcriptase inhibitor-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic black persons with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (odds ratio, 3.7 [95% confidence interval, 1.1-12.0]). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to nucleoside reverse-transcriptase inhibitor-associated toxicity.
先前的研究表明,在使用核苷逆转录酶抑制剂进行抗逆转录病毒治疗期间,外周神经病变易感性与非西班牙裔白种人群中的欧洲线粒体 DNA(mtDNA)单倍群有关。为了确定核苷逆转录酶抑制剂相关的外周神经病变是否与非西班牙裔黑人群体中的 mtDNA 变异有关,我们对艾滋病临床试验组研究 384 的参与者的 mtDNA 进行了测序。在有基因组数据的 156 名非西班牙裔黑人中,有 51 名(33%)发生了外周神经病变。在多变量模型中,非洲 mtDNA 亚单倍群 L1c 是外周神经病变的独立预测因子(比值比,3.7 [95%置信区间,1.1-12.0])。这是首次有研究表明非洲 mtDNA 亚单倍群与核苷逆转录酶抑制剂相关毒性的易感性有关。